chr14-60964898-T-C

Variant names:

• chr14-60964898-T-C
• rs8012779
• NM_002431.4:c.810-3331T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002431.4(MNAT1):​c.810-3331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,236 control chromosomes in the GnomAD database, including 63,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63790 hom., cov: 32)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 5 publications found

Genes affected

MNAT1 (HGNC:7181): (MNAT1 component of CDK activating kinase) The protein encoded by this gene, along with cyclin H and CDK7, forms the CDK-activating kinase (CAK) enzymatic complex. This complex activates several cyclin-associated kinases and can also associate with TFIIH to activate transcription by RNA polymerase II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000258892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.810-3331T>C		intron_variant	Intron 7 of 7	ENST00000261245.9	NP_002422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.810-3331T>C		intron_variant	Intron 7 of 7	1	NM_002431.4	ENSP00000261245.4

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138596 AN: 152118 Hom.: 63752 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.917

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.911 AC: 138692 AN: 152236 Hom.: 63790 Cov.: 32 AF XY: 0.907 AC XY: 67541 AN XY: 74438

African (AFR) AF: 0.806 AC: 33456 AN: 41494

American (AMR) AF: 0.878 AC: 13430 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3291 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4101 AN: 5192

South Asian (SAS) AF: 0.767 AC: 3695 AN: 4820

European-Finnish (FIN) AF: 0.990 AC: 10493 AN: 10604

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67108 AN: 68036

Other (OTH) AF: 0.913 AC: 1931 AN: 2116

Alfa AF: 0.958 Hom.: 279900

Bravo AF: 0.901

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8012779; hg19: chr14-61431616;